Article (Scientific journals)
Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn's disease: report of the OPERA study.
Sandborn, William J.; Lee, Scott D.; Tarabar, Dino et al.
2018In Gut
Peer Reviewed verified by ORBi
 

Files


Full Text
2017_Phase II evaluation of anti-MAdCAM antibody...OPERA study_Gut_PPE.pdf
Publisher postprint (1.12 MB)
Download

Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd (& BSG) under licence.


All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
crohn's disease; inflammatory bowel disease; integrins; pharmacotherapy
Abstract :
[en] OBJECTIVE: This phase II, randomised, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PF-00547659, a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule (MAdCAM) to selectively reduce lymphocyte homing to the intestinal tract, in patients with moderate-to-severe Crohn's disease (CD). DESIGN: Eligible adults were aged 18-75 years, with active moderate-to-severe CD (Crohn's Disease Activity Index (CDAI) 220-450), a history of failure or intolerance to antitumour necrosis factor and/or immunosuppressive agents, high-sensitivity C reactive protein >3.0 mg/L and ulcers on colonoscopy. Patients were randomised to PF-00547659 22.5 mg, 75 mg or 225 mg or placebo. The primary endpoint was CDAI 70-point decrease from baseline (CDAI-70) at week 8 or 12. RESULTS: In all, 265 patients were eligible for study entry. Although CDAI-70 response was not significantly different with placebo versus PF-00547659 treatment at weeks 8 or 12, remission rate was greater in patients with higher baseline C reactive protein (>5 mg/L vs >18.8 mg/L, respectively). Soluble MAdCAM decreased significantly from baseline to week 2 in a dose-related manner and remained low during the study in PF-00547659-treated patients. Circulating beta7+ CD4+ central memory T-lymphocytes increased at weeks 8 and 12 with PF-00547659 treatment. No safety signal was seen. CONCLUSIONS: Clinical endpoint differences between PF-00547659 and placebo did not reach statistical significance in patients with moderate-to-severe CD. PF-00547659 was pharmacologically active, as shown by a sustained dose-related decrease in soluble MAdCAM and a dose-related increase in circulating beta7+ central memory T cells. TRIAL REGISTRATION NUMBER: NCT01276509; Results.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Sandborn, William J.
Lee, Scott D.
Tarabar, Dino
Louis, Edouard  ;  Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Klopocka, Maria
Klaus, Jochen
Reinisch, Walter
Hebuterne, Xavier
Park, Dong-Il
Schreiber, Stefan
Nayak, Satyaprakash
Ahmad, Alaa
Banerjee, Anindita
Brown, Lisa S.
Cataldi, Fabio
Gorelick, Kenneth J.
Cheng, John B.
Hassan-Zahraee, Mina
Clare, Robert
D'Haens, Geert R.
More authors (10 more) Less
Language :
English
Title :
Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn's disease: report of the OPERA study.
Publication date :
2018
Journal title :
Gut
ISSN :
0017-5749
eISSN :
1468-3288
Publisher :
BMJ Publishing Group, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Additional URL :
Commentary :
(c) Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Available on ORBi :
since 07 December 2017

Statistics


Number of views
158 (1 by ULiège)
Number of downloads
187 (1 by ULiège)

Scopus citations®
 
90
Scopus citations®
without self-citations
82
OpenCitations
 
68

Bibliography


Similar publications



Contact ORBi